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Glycobiology Advance Access originally published online on November 15, 2007
Glycobiology 2008 18(1):28-41; doi:10.1093/glycob/cwm125
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© 2007 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Altered glycosylation of recombinant NKp30 hampers binding to heparan sulfate: a lesson for the use of recombinant immunoreceptors as an immunological tool

Oren Hershkovitz2, Mostafa Jarahian4, Alon Zilka2, Ahuva Bar-Ilan2, Guy Landau2, Sergey Jivov2, Yoram Tekoah3, Rachel Glicklis3, John T. Gallagher6, Sabrina C. Hoffmann5, Hagit Zer7, Ofer Mandelboim8, Carsten Watzl5, Frank Momburg4 and Angel Porgador1,2

2 The Shraga Segal Department of Microbiology and Immunology, Faculty of Health Sciences and the Cancer Research Center; and
3 Center for Glycobiology, Department of Biotechnology Engineering, Ben-Gurion University of the Negev, Beer-Sheva, 84105, Israel
4 Division of Molecular Immunology, German Cancer Research Center
5 Institute for Immunology, University of Heidelberg, Im Neuenheimer Feld 305, 69120 Heidelberg, Germany
6 Department of Medical Oncology, University of Manchester, Cancer Research UK, Christie, Hospital NHS Trust, Manchester M204BX, UK
7 Biacore Laboratory, Interdepartmental Equipment Unit, Institute of Life Sciences
8 The Lautenberg Center for General and Tumor Immuno- logy, Hebrew University—Hadassah Medical School, Jerusalem, Israel

1 To whom correspondence should be addressed: Tel: +972-8-647-7283; Fax: +972-8-647-2574; e-mail: angel{at}bgu.ac.il

Received on April 4, 2007; revised on November 5, 2007; accepted on November 5, 2007

NKp30 is a natural cytotoxicity receptor expressed by human NK cells and involved in NK lytic activity. We previously published that membranal heparan sulfate serves as a coligand for human NKp30. In the present study, we complement our results by showing direct binding of recombinant NKp30 to immobilized heparin. The heparan sulfate epitope(s) on target tumor cells and the heparin epitope(s) recognized by NKp30 share similar characteristics. Warren and colleagues (Warren HS, Jones AL, Freeman C, Bettadapura J, Parish CR. 2005. Evidence that the cellular ligand for the human NK cell activation receptor NKp30 is not a heparan sulfate glycosaminoglycan. J Immunol. 175:207–212) published that NKp30 does not bind to membranal heparan sulfate on target cells and that heparan sulfate is not involved in NKp30-mediated lysis. In the current study, we examine the binding of six different recombinant NKp30s to membranal heparan sulfate and conclude that NKp30 does interact with membranal heparan sulfate. Yet, two of the six recombinant NKp30s, including the commercially available recombinant NKp30 (employed by Warren et al.) did not show heparan sulfate-dependent binding. We demonstrate that this is due to an altered glycosylation of these two recombinant NKp30s. Upon removal of its N-linked glycans, heparan sulfate-dependent binding to tumor cells and direct binding to heparin were restored. Overall, our results emphasize the importance of proper glycosylation for analysis of NKp30 binding to its ligand and that membranal heparan sulfate could serve as a coligand for NKp30. At the cellular level, soluble heparan sulfate enhanced the secretion of IFN{gamma} by NK-92 natural killer cells activated with anti-NKp30 monoclonal antibody. We discuss the involvement of heparan sulfate binding to NKp30 in NKp30-mediated activation of NK cells.

Key words: glycosylation / heparan sulfate / natural killer / NCR / NKp30


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